This Program Project is a multidisciplinary program targeted to evaluate new means of early diagnosis and therapy of human cancer. Human tumors of neural crest origin including melanoma, soudomas, and glioblastomas are a primary focus of this grant. We have had recent success in developing monoclonal antibody to human pancreatic tumor associated antigens and work is proposed to expand this area in terms of immunodiagnosis and therapy of this difficult malignancy. We have developed murine hybridomas and are at present extending these studies towards producing human-human hybridomas for the production of monoclonal antibodies reactive with insulinoma, pancreatic carcinoma, and human melanoma. These monoclonal antibodies will be utilized in our studies of both experimental and human radionuclide imaging. The monoclonal antibodies will also be used in experimental and clinical trials as passive serotherapy for the aforementioned malignancies. We have been successful in experimental models in the utilization of murine retroviruses for alteration of both antigenicity and immunogenicity of murine sarcomas. We have recently infected human melanoma cells with murine retrovirus. This now provides us an ideal experimental model for evaluating the altered host response to this human tumor cell. Phase I clinical trials are proposed in patients with metastatic melanoma who have failed all conventional therapies. In this study we will evaluate the possible therapeutic benefit of either anti-viral antibody alone, monoclonal anti-melanoma antibody alone or the two antibodies administered together for possible synergistic effect.